Methods for improving sleep efficiency in healthy human beings

ABSTRACT

Embodiments of the invention generally relate to methods and supplements for improving sleep efficiency in human beings.

TECHNICAL FIELD

Embodiments of the invention generally relate to methods and supplementsfor improving sleep efficiency in healthy humans.

BACKGROUND

A circadian rhythm is any biological process that displays anendogenous, entrainable oscillation of about 24 hours. These rhythms aredriven by a circadian clock, and rhythms have been widely observed inplants, animals, fungi and cyanobacteria. The term circadian comes fromthe Latin circa, meaning “around” (or “approximately”), and diem ordies, meaning “day”. The formal study of biological temporal rhythms,such as daily, tidal, weekly, seasonal, and annual rhythms, is calledchronobiology. Although circadian rhythms are endogenous (“built-in”,self-sustained), they are adjusted (entrained) to the local environmentby external cues called zeitgebers, commonly the most important of whichis daylight.

Circadian rhythmicity is present in the sleeping and feeding patterns ofanimals, including human beings. There are also clear patterns of corebody temperature, brain wave activity, hormone production, cellregeneration and other biological activities. In addition,photoperiodism, the physiological reaction of organisms to the length ofday or night, is vital to both plants and animals, and the circadiansystem plays a role in the measurement and interpretation of day length.The primary circadian “clock” in mammals is located in thesuprachiasmatic nucleus (or nuclei) (SCN), a pair of distinct groups ofcells located in the hypothalamus. The SCN receives information aboutillumination through the eyes. The retina of the eye contains“classical” photoreceptors (“rods” and “cones”), which are used forconventional vision. But the retina also contains specialized ganglioncells which are directly photosensitive, and project directly to the SCNwhere they help in the entrainment of this master circadian clock.

These cells contain the photopigment melanopsin and their signals followa pathway called the retinohypothalamic tract, leading to the SCN. Ifcells from the SCN are removed and cultured, they maintain their ownrhythm in the absence of external cues.

The SCN takes the information on the lengths of the day and night fromthe retina, interprets it, and passes it on to the pineal gland, a tinystructure shaped like a pine cone and located on the epithalamus. Inresponse, the pineal secretes the hormone melatonin. Secretion ofmelatonin peaks at night and ebbs during the day and its presenceprovides information about night-length.

Several studies have indicated that pineal melatonin feeds back on SCNrhythmicity to modulate circadian patterns of activity and otherprocesses. However, the nature and system-level significance of thisfeedback are unknown.

It would be desirable to provide a nutritional supplement for improvingsleep efficiency in healthy humans.

BRIEF SUMMARY OF THE INVENTION

Described herein are nutritional supplement and method of using thesame. The nutritional supplement includes an amino acid secretagoguecomposition, which, taken orally, stimulates the pituitary gland torelease hGH.

Some embodiments include an oral nutritional supplement that comprisesL-arginine, oxo-proline, and L-lysine.

A particular embodiment of the present disclosure relates to an oralnutritional supplement that includes the amino acids 1-lysine,1-arginine, oxo-proline, and one of either cysteine or glutamine. Theamino acids may be delivered as non-toxic salts thereof, effectivecomplexes thereof, stable chelates thereof, active esters thereof,functional derivatives thereof, and mixtures thereof which are effectiveto increase hGH levels in the general population.

Another particular embodiment relates to an oral nutritional supplementthat consists essentially of 1-lysine HCl, 1-arginine HCl, oxo-proline,N-acetyl-1-cysteine, 1-glutamine, and schizonepeta (aerial parts)powder.

Other embodiments are drawn to methods of increasing human growthhormone in humans that include orally administering the disclosednutritional supplement to a healthy human being.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows a linear regression analysis of time to fall asleep withcontinued use of the supplement over time; and

FIG. 2 shows time awake during sleep over time with continued use of thesupplement.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a nutritional supplement for use by ahuman being. The supplement of the present invention works as a dietarysupplement by assisting the body's own ability to improve sleepefficiency naturally in a manner which is safe and effective, as well asbeing affordable.

A particular embodiment of the present disclosure relates to an oralnutritional supplement that includes 1-lysine, 1-arginine, oxo-proline,and one of either cysteine or glutamine. The supplement may additionallyinclude both cysteine and glutamine and/or schizonepeta powder. Inparticular embodiments, a functional dosage includes the 1-arginine at alevel between 0.1-6 mmol and the oxo-proline between 0.1-8 mmol, and/orthe 1-lysine in an amount between 0.1-12 mmol. The cysteine and/orglutamine may be contained at a level between 0.001-6 mmol. In anotherparticular embodiment, a functional dosage includes the 1-arginine at alevel between 2.5-4.5 mmol and the oxo-proline between 4-6 mmol, and/orthe 1-lysine in an amount between 7-9 mmol. The cysteine and/orglutamine may be contained at a level between 0.001-0.5 mmol. Thecysteine can be n-acetyl L-cysteine and the glutamine may be1-glutamine. The amino acids may be delivered as non-toxic saltsthereof, effective complexes thereof, stable chelates thereof, activeesters thereof, functional derivatives thereof, and mixtures thereofwhich are effective to increase hGH levels in the general population.The nutritional supplement may be present in an amount of 2.9 grams. Thenutritional supplement may be in any acceptable and known oralformulation, such as powder, tablet, capsule, liquid, or wafer form.

Another particular embodiment relates to an oral nutritional supplementthat consists essentially of 1-lysine HCl, 1-arginine HCl, oxo-proline,N-acetyl-1-cysteine, 1-glutamine, and schizonepeta (aerial parts)powder. In particular embodiments, a functional dosage includes the1-arginine HCl at a level between 0.1-6 mmol and the oxo-proline between0.1-8 mmol, and/or the 1-lysine HCl in an amount between 0.1-12 mmol.The n-acetyl L-cysteine and/or 1-glutamine may be contained at a levelbetween 0.001-6 mmol. In another particular embodiment, a functionaldosage includes the 1-arginine HCl at a level between 2.5-4.5 mmol andthe oxo-proline between 4-6 mmol, and/or the 1-lysine HCl in an amountbetween 7-9 mmol. The n-acetyl L-cysteine and/or 1-glutamine may becontained at a level between 0.001-0.5 mmol. The nutritional supplementmay be in any acceptable and known oral formulation, such as powder,tablet, capsule, liquid, or wafer form.

Other embodiments are drawn to methods of increasing human growthhormone in humans that include orally administering the disclosednutritional supplement to a healthy human being. As used herein,“healthy human being” means a human being without any physiologicaldeficiency in hGH independent of age. Particular embodiments of theinvention relate to oral administration of the disclosed nutritionalsupplement to a human that is at least 30 years old. The nutritionalsupplement may be administered from one to three times daily or,alternatively, may be administered every other day, or may beadministered once a week. In particular embodiments, the nutritionalsupplement may be administered on an empty stomach.

In accordance with the “consist essentially of” and “consistingessentially of” language, the nutritional supplement of the thirdembodiments is essentially limited to the aforementioned ingredients anddoes not include any additional active ingredients intended to addnutritional content (e.g., vitamins, minerals, etc.), but may includeadditional ingredients not intended to add nutritional content such asingredients intended to fulfill a non-nutritional purpose (e.g.,coloring, fillers, flavoring, an ingredient for maintaining thestructural form, etc.).

Each ingredient of the nutritional supplement of the present inventionmay be prepared in accordance with any method known to one of ordinaryskill in the art. Alternatively, each ingredient may be obtained in afully prepared from a commercially available source.

The nutritional supplement of the present invention may be in anysuitable oral administration form, including but not limited to: achewable form, a liquid form, a spray form, a capsule form, asuppository form, dissolvable wafer, and a powder form.

Irrespective of the structural form of the nutritional supplement, theingredients of the nutritional supplement may be distributedhomogeneously or non-homogeneously within the nutritional supplement.

The nutritional supplement of the present invention may be ingested on aregular basis, such as a daily or weekly intake at a dosage tailored toan individual's needs; i.e., the nutritional supplement is to be takenregularly as multiples (1×, 2×, etc.) of the structural units (pills,tablets, capsules, liquid dose, etc.) in accordance with the needs ofthe individual. For example, a senior citizen leading a sedentary lifemay need higher daily doses than does a young person engaged in regularstrenuous exercise (e.g., a weight lifter). Alternatively, thenutritional supplement of the present invention may be ingested on anas-needed basis at a dosage tailored to the individual's needs. Medicalor nutritional counseling may be beneficial for arriving at a desirableor optimal dosage tailored to the individual's needs.

The combination of types of amino acids, mass ranges, and specificformulations have been selected to be synergistically balanced and ofadequate quantity to achieve the desired physiological effect, namely,improving sleep efficiency. Improper combinations of the amino acids maybe ineffective. The component amino acids are synergistic in the sensethat several of them when combined together, synergistically improvesleep efficiency. The combination was also chosen to reduce or inhibitchemical combination or reaction between the amino acids.

EXAMPLES

A double-blind clinical study involved 15 healthy subjects [10 males, 5females; mean age=33±7 years]. Each subject completed a baseline EpworthSleepiness Scale self-report questionnaire and a standardized assay ofusual sleep habits. All subjects were deemed to have average sleepparameters within a normal range.

The subjects were then provided a three week supply of a novelsupplement SeroVital (2.9 g/dose blend of 1-lysine HCl, 1-arginine HCl,oxo-proline, N-acetyl-1-cysteine, 1-glutamine, and schizonepeta (aerialparts) powder). The novel SeroVital blend has been shown previously toincrease serum human growth hormone hGH levels by 8 times (equivalent to682%) 120 minutes after a single dose in healthy male and femalevolunteers. Because night-time onset of hGH has been directly correlatedto sleep efficiency, we investigated sleep patterns with continued useof the supplement when taken on an empty stomach, two hours after dinnerprior to bedtime, every night for three weeks. On each trial day,subjects reported 1) time went to bed; 2) time of final wakening; 3)estimated time to fall asleep; 4) time of awakening during sleep/lengthof time awake. Data was compiled by day for estimated time to fallasleep and length of time awake during sleep in order to assess sleepefficiency. Daily values for each measure were plotted as an average(±S.D.) among the subjects over the time course of the study, and alinear regression was tabulated to assess overall trends over time. Allavailable data was included in the analysis.

Linear regression analysis showed that both estimated time to fallasleep (FIG. 1) and time awake during sleep (FIG. 2) tended to decreaseover time with continued use of the supplement over the time course ofthe study. Time to fall asleep decreased with an average slope of −0.24min/day, and time awake during sleep decreased by an average slope of−0.26 min/day. Overall, these results so a trend towards greater sleepefficiency by measurements of both time to fall asleep and time awakeduring sleep, both with a quantified average decrease of about 0.25min/day over three weeks with regular nighttime use of the novelSeroVital supplement (when taken as directed, on an empty stomach, twohours after dinner prior to bedtime).

While embodiments of the present invention have been described hereinfor purposes of illustration, many modifications and changes will becomeapparent to those skilled in the art. Accordingly, the appended claimsare intended to encompass all such modifications and changes as fallwithin the true spirit and scope of this invention.

We claim:
 1. A method of improving sleep efficiency in a healthy humanbeing in need thereof, comprising: providing a nutritional supplementcomposition in unit dosage form, wherein the unit dosage consists of:about 1 mmol L-arginine; about 1 mmol Oxo-proline; about 2 mmolL-lysine; about 1.5 μmol N-acetyl L-cysteine; about 2 μmol L-glutamine;and about 125 μg Schizonepta (aerial parts) powder; and orallyadministering an effective amount of the nutritional supplementcomposition to the human being.
 2. The method of claim 1, where theeffective amount of the nutritional supplement composition is 2.9 grams.3. The method of claim 1, wherein the nutritional supplement compositionis in powder, tablet, capsule, liquid or wafer form.
 4. The method ofclaim 1, wherein orally administering the nutritional supplementcomposition to a healthy human being comprises orally administering thenutritional supplement composition to the human being from one to threetimes daily.
 5. The method of claim 1, wherein orally administering thenutritional supplement composition to a healthy human being comprisesorally administering the nutritional supplement composition to the humanbeing once a week.
 6. The method of claim 1, wherein orallyadministering the nutritional supplement composition to a healthy humanbeing comprises orally administering the nutritional supplementcomposition to the human being on an empty stomach.
 7. The method ofclaim 1, wherein the healthy human being is a female human being.
 8. Amethod of improving sleep efficiency in a healthy human being in needthereof, comprising: providing a nutritional supplement composition inunit dosage form, wherein unit dosage form consists of: 0.86 mmolL-arginine; 1.32 mmol Oxo-proline; 2.05 mmol L-lysine; 1.53 μmolN-acetyl L-cysteine; 1.71 μmol L-glutamine; and 125 μg Schizonepta(aerial parts) powder and orally administering an effective amount ofthe nutritional supplement composition to the human being.
 9. The methodof claim 8, wherein the unit dosage form consists of 181.38 mgL-arginine HCl; 170.93 mg L-pyroglutamic acid; 374.83 mg L-lysine HCl;0.25 mg N-acetyl L-cysteine USP; 0.25 mg L-glutamine; and 0.125 mgSchizonepta (aerial parts) powder.
 10. A method of improving sleepefficiency in a healthy human being in need thereof, comprising:providing a serving of the nutritional supplement composition in unitdosage form, wherein the unit dosage form consists of: 3.44 mmolL-arginine; 5.30 mmol Oxo-proline; 8.21 mmol L-lysine; 6.13 μmolN-acetyl L-cysteine; 6.84 μmol L-glutamine; and 0.50 mg Schizonepta(aerial parts) powder; and orally administering an effective amount ofthe nutritional supplement composition to the healthy human being. 11.The method of claim 10, wherein the unit dosage form consists of 725.50mg L-arginine HCl; 683.70 mg L-pyroglutamic acid; 1499.30 mg L-lysineHCl; 1.00 mg N-acetyl L-cysteine USP; 1.00 mg L-glutamine; and 0.50 mgSchizonepta (aerial parts) powder.
 12. The method of claim 10, where theeffective amount of the nutritional supplement composition is 2.9 grams.13. The method of claim 10, wherein the nutritional supplementcomposition is in powder, tablet, capsule, liquid or wafer form.
 14. Themethod of claim 10, wherein orally administering the nutritionalsupplement composition to a healthy human being comprises orallyadministering the nutritional supplement composition to the human beingfrom one to three times daily.
 15. The method of claim 10, whereinorally administering the nutritional supplement composition to a healthyhuman being comprises orally administering the nutritional supplementcomposition to the human being once a week.
 16. The method of claim 10,wherein orally administering the nutritional supplement composition to ahealthy human being comprises orally administering the nutritionalsupplement composition to the human being on an empty stomach.
 17. Themethod of claim 10, where the healthy human being is at least 30 yearsold.